Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome

Orphanet Journal of Rare Diseases

Ingrid Øra¹  Jacek Toporski⁵  Dominik Turkiewicz⁵  Albert N Békássy⁵  Jan-Eric Månsson²  Domniki Papadopoulou⁶  Erik A Eklund⁴  Julia Larsson³  Sandra Jester³ 

[1] Department of Oncogenomics, Academic Medical Center, University of Amsterdam, The Netherlands;Department of Clinical Chemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden;Section for Experimental Pediatrics, Clinical Sciences, Lund University, Lund, Sweden;Department of Pediatric Oncology and Hematology, Skåne University Hospital, Lund, Sweden;Department of Pediatric Endocrinology, Skåne University Hospital, Lund, Sweden

关键词: Clinical outcome;    Haploidentical stem cell transplantation;    Mucopolysaccharidosis VI;   

Others  :  863573
DOI  :  10.1186/1750-1172-8-134

 received in 2013-05-26, accepted in 2013-08-28,  发布年份 2013

【 摘 要 】

Background

Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option.

This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome.

Patients and methods

Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p.C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT.

Results

Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 μkat/kg protein (patient 1) and from 3.6 to 17.9 μkat/kg protein (patient 2) (ref. 17–40). Total urinary GAG normalized in both patients, although patient 2’s values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae.

Conclusion

This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT.

【 授权许可】

   
2013 Jester et al.; licensee BioMed Central Ltd.

【 图 表 】

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